Patent SG-11201807022X-A (SG)
Title: Recombinant mva or mvadele3l expressing human flt3l and use thereof as immuno-therapeutic agents against solid tumors
Inventor: DENG LIANG
IPC: C07K14/07
Filed: 2017-02-25
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property -, Organization M1111101110101011111 HO 1111101110101110111 Ell 100 HI 111110111100# 11 International Bureau .. .... ..Yejd ..... ....!;,, (10) International Publication Number (43) International Publication Date WO 2017/147554 A3 31 August 2017 (31.08.2017) WIPO I PCT (51) International Patent Classification: Center, 1275 York Avenue, New York, NY 10021 (US). A61K 39/12 (2006.01) CO7K 14/005 (2006.01) YANG, Ning; c/o Memorial Sloan-Kettering Cancer Cen- A61K 39/285 (2006.01) C07K 14/07 (2006.01) ter, 1275 York Avenue, New York, NY 10021 (US). (21) International Application Number: (74) Agents: FERNANDES, Jolene, S. et al.; Foley & Lardner PCT/US2017/019549 LLP, 3000 K Street, Suite 600, Washington, DC 20007- 5109 (US). (22) International Filing Date: 25 February 2017 (25.02.2017) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (25) Filing Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (26) Publication Language: English BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (30) Priority Data: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, 62/300,066 25 February 2016 (25.02.2016) US KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, 62/418,786 7 November 2016 (07.11.2016) US MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, 62/418,788 8 November 2016 (08.11.2016) US NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, (71) Applicant: MEMORIAL SLOAN-KETTERING CAN- RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, CER CENTER [US/US]; 1275 York Avenue, New York, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, NY 10021 (US). ZA, ZM, ZW. (72) Inventors: DENG, Liang; c/o Memorial Sloan-Kettering (84) Designated States (unless otherwise indicated, for every _ Cancer Center, 1275 York Avenue, New York, NY 10021 kind of regional protection available): ARIPO (BW, GH, = GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, = (US). SHUMAN, Stewart; c/o Memorial Sloan-Kettering TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, = Cancer Center, 1275 York Avenue, New York, NY 10021 TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, _ (US). WOLCHOK, Jedd; c/o Memorial Sloan-Kettering = Cancer Center, 1275 York Avenue, New York, NY 10021 DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, MERGHOUB, Taha; Memorial Sloan-Kettering LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (US). c/o SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, Cancer Center, 1275 York Avenue, New York, NY 10021 = WANG, Weiyi; Memorial Sloan-Kettering Can- GW, KM, ML, MR, NE, SN, TD, TG). = (US). c/o — cer Center, 1275 York Avenue, New York, NY 10021 (US). DAI, Peihong; c/o Memorial Sloan-Kettering Cancer = [Continued on next page] (54) Title: RECOMBINANT MVA OR MVADELE3L EXPRESSING HUMAN FLT3L AND USE THEREOF AS IM- - MUNO-THERAPEUTIC AGENTS AGAINST SOLID TUMORS = Figure 1 = = = Schematic diagram of homologous recombination at the TK locus = — pCB vector TK -L SG PSE7L P7.5 9Pt TK-R = SGSGR VG pCB-R2 -F MVA _ genome TK-1. TK-R 4 4 M TK genomic region PCR (1) TK-F2/pCB-R3 Homologous recombination (HR) 71' (2) TK-F4/TK R4 TK deletion ON ir) (3) SG-FIR Specific Gene (SG) ir) (4) TK-F5/TK-R5 Sequencing specific gene insertion (Seq) IN 71' li L .. ' (57) : The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it ::::; concerns the use of a recombinant modified vaccinia Ankara (MVA) virus comprising an MVA harboring a human Fms-like tyrosine N kinase 3 ligand (hFlt3L) (MVA-hFtl3L). The foregoing vaccinia Ankara (MVA) virus can be delivered to tumor cells of a subject at- 0 flicted with a malignant solid tumor, to treat the tumor. In a related aspect, the present disclosure concerns a recombinant modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MV At.E3L) modified to express human Fms-like 5 tyrosine kinase 3 ligand (hFlt3L) isolated, suitable for use as an immunotherapeutic agent against a malignant solid tumor. WO 2017/147554 A3 I Hi IOME °MOEN ME II M 010 VIII EDE IIIII IIII111110111 00# Published: — with sequence listing part of description (Rule 5.2(a)) — with international search report (Art. 2 1 (3)) (88) Date of publication of the international search report: — before the expiration of the time limit for amending claims and to be republished in the event of receipt amendments (Rule 48.2(h)) the of 19 October 2017